1. Field of Invention
The present invention relates to TAB1 protein which forms a part of the signal-transduction pathway of Transforming Growth Factor-.beta. (TGF.beta.), and to a gene coding therefor.
2. Related Art
TGF-.beta. is a multifunctional factor which regulates various cellular functions. As one of those functions, TGF-.beta. is responsible for the repair and reproduction of tissues with various types of injury.
Abnormal production of TGF-.beta. in cases of chronic injury sometimes results in an imbalance between the repair and the reproduction of tissues and thus pathological fibrosis. Hepatic fibrosis is known as one condition resulting from an imbalance in TGF-.beta. production. In the liver, TGF-.beta. accelerates production of extracellular matrix proteins which are responsible for fibrosis, while inhibiting synthesis of extracellular matrix protein catabolic enzymes and inducing catabolic enzyme inhibitors, and it thus acts as a major causative factor of hepatic fibrosis.
One of known members of signal-transduction pathway belonging to the TGF-.beta. superfamily is the Mitogen-Activated Protein Kinase Kinase Kinase (MAPKKK) system.
The MAPK pathway is a conserved eukaryotic signal-transduction pathway which converts receptor signals into various functions, and the system comprises 3 different protein kinases, specifically MAPKKK mentioned above, MAPKK and MAPK, with MAPK being activated through phosphorylation by MAPKK, and MAPKK in turn being activated by MAPKKK (E. Nishida et al., Trends Biochem. Sci. Vol.18, p.128 (1993); K. J. Blumer et al, op. cit. Vol.19, p.236 (1994); R. J. David, op. cit. Vol.19, p.470 (1994); C. J. Marchall, Cell, Vol.80, p.179 (1995)).
TAK1, which is a member of the MAPKKK family which functions in signal-transduction pathways belonging to the TGF-.beta. superfamily, has been identified by K. Yamaguchi (K. Yamaguchi et al., Science, Vol.270, p.2008 (1995)).
TGF-.beta. transduces signal through a heteromeric complex of type I and type II TGF-.beta. receptors, which are transmembrane proteins comprising cytoplasmic serine- and threonine-specific kinase domains (J. L. Wrana et al., Nature, Vol.370, p.341 (1994); D. M. Kingsley et al., Genes Dev., Vol.8, p.133 (1994)). However, little is known at the molecular level about the signal-transduction mechanism downstream from the TGF-.beta. receptors.